Is OCRL p.Arg663Leu (c.1988G>T) pathogenic?

OCRL p.Arg663Leu (c.1988G>T) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 2 submitters; last evaluated 2020-03-17). AlphaMissense: likely pathogenic (0.6798); Absent from gnomAD v4.1; Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Arg663Leu (c.1988G>T)?

OCRL p.Arg663Leu (c.1988G>T) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg663Leu (c.1988G>T) in the general population?

OCRL p.Arg663Leu (c.1988G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Arg663Leu (c.1988G>T)?

AlphaMissense predicts likely pathogenic (score 0.6798) — an in-silico prediction, not a clinical call.

OCRL p.Arg663Leu

c.1988G>T · rs745885693 · VCV1003381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6798 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.6798	likely pathogenic
REVEL	0.278	benign-leaning
SaProt	LLR -10.58	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 2.7, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OCRL
Protein: p.Arg663Leu
Coding: c.1988G>T
MANE Select: NM_000276
dbSNP: rs745885693
Type: single nucleotide variant
Location: chrX:129576425 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 663: the 'ash' region

Full OCRL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

oculocerebrorenal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OCRL p.Arg663Ter Pathogenic ★★ same residue
OCRL p.Arg663Gln Uncertain significance ★ ⚠ same residue
OCRL c.1244+1G>A Pathogenic/Likely pathogenic ★★ same condition
OCRL c.1714-1G>A Pathogenic ★★ same condition
OCRL c.2256+1G>T Likely pathogenic ★★ same condition
OCRL c.560+1G>C Pathogenic/Likely pathogenic ★★ same condition
OCRL c.940-11G>A Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Ala861Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ocrl-p-arg663leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown